Prediction of regulatory targets of alternative isoforms of the epidermal growth factor receptor in a glioblastoma cell line.

BackgroundThe epidermal growth factor receptor (EGFR) is a major regulator of proliferation in tumor cells. Elevated expression levels of EGFR are associated with prognosis and clinical outcomes of patients in a variety of tumor types. There are at least four splice variants of the mRNA encoding four protein isoforms of EGFR in humans, named I through IV. EGFR isoform I is the full-length protein, whereas isoforms II-IV are shorter protein isoforms. Nevertheless, all EGFR isoforms bind the epidermal growth factor (EGF). Although EGFR is an essential target of long-established and successful tumor therapeutics, the exact function and biomarker potential of alternative EGFR isoforms II-IV are unclear, motivating more in-depth analyses. Hence, we analyzed transcriptome data from glioblastoma cell line SF767 to predict target genes regulated by EGFR isoforms II-IV, but not by EGFR isoform I nor other receptors such as HER2, HER3, or HER4.ResultsWe analyzed the differential expression of potential target genes in a glioblastoma cell line in two nested RNAi experimental conditions and one negative control, contrasting expression with EGF stimulation against expression without EGF stimulation. In one RNAi experiment, we selectively knocked down EGFR splice variant I, while in the other we knocked down all four EGFR splice variants, so the associated effects of EGFR II-IV knock-down can only be inferred indirectly. For this type of nested experimental design, we developed a two-step bioinformatics approach based on the Bayesian Information Criterion for predicting putative target genes of EGFR isoforms II-IV. Finally, we experimentally validated a set of six putative target genes, and we found that qPCR validations confirmed the predictions in all cases.ConclusionsBy performing RNAi experiments for three poorly investigated EGFR isoforms, we were able to successfully predict 1140 putative target genes specifically regulated by EGFR isoforms II-IV using the developed Bayesian Gene Selection Criterion (BGSC) approach. This approach is easily utilizable for the analysis of data of other nested experimental designs, and we provide an implementation in R that is easily adaptable to similar data or experimental designs together with all raw datasets used in this study in the BGSC repository, https://github.com/GrosseLab/BGSC

Plasmodium falciparum Malaria and Atovaquone-Proguanil Treatment Failure

We noticed overrepresentation of atovaquone-proguanil therapeutic failures among Plasmodium falciparum–infected travelers weighing >100 kg. We report here 1 of these cases, which was not due to resistant parasites or impaired drug bioavailability. The follow-up of such patients should be strengthened

The Spitzer c2d Survey of Weak-line T Tauri Stars II: New Constraints on the Timescale for Planet Building

One of the central goals of the Spitzer Legacy Project ``From Molecular Cores to Planet-forming Disks'' (c2d) is to determine the frequency of remnant circumstellar disks around weak-line T Tauri stars (wTTs) and to study the properties and evolutionary status of these disks. Here we present a census of disks for a sample of over 230 spectroscopically identified wTTs located in the c2d IRAC (3.6, 4.5, 4.8, and 8.0 um) and MIPS (24 um) maps of the Ophiuchus, Lupus, and Perseus Molecular Clouds. We find that ~20% of the wTTs in a magnitude limited subsample have noticeable IR-excesses at IRAC wavelengths indicating the presence of a circumstellar disk. The disk frequencies we find in these 3 regions are ~3-6 times larger than that recently found for a sample of 83 relatively isolated wTTs located, for the most part, outside the highest extinction regions covered by the c2d IRAC and MIPS maps. The disk fractions we find are more consistent with those obtained in recent Spitzer studies of wTTs in young clusters such as IC 348 and Tr 37. From their location in the H-R diagram, we find that, in our sample, the wTTs with excesses are among the younger part of the age distribution. Still, up to ~50% of the apparently youngest stars in the sample show no evidence of IR excess, suggesting that the circumstellar disks of a sizable fraction of pre-main-sequence stars dissipate in a timescale of ~1 Myr. We also find that none of the stars in our sample apparently older than ~10 Myrs have detectable circumstellar disks at wavelengths < 24 um. Also, we find that the wTTs disks in our sample exhibit a wide range of properties (SED morphology, inner radius, L_DISK/L*, etc) which bridge the gaps observed between the cTTs and the debris disk regimes.Comment: 54 pages, 13 figures, Accepted by Ap

A Case of Urogenital Human Schistosomiasis from a Non-endemic Area

© 2015 Calvo-Cano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Detection of Strong Millimeter Emission from the Circumstellar Dust Disk Around V1094 Sco: Cold and Massive Disk around a T Tauri Star in a Quiescent Accretion Phase?

We present the discovery of a cold massive dust disk around the T Tauri star V1094 Sco in the Lupus molecular cloud from the 1.1 millimeter continuum observations with AzTEC on ASTE. A compact ($r\lesssim$320 AU) continuum emission coincides with the stellar position having a flux density of 272 mJy which is largest among T Tauri stars in Lupus. We also present the detection of molecular gas associated with the star in the five-point observations in $^{12}$CO J=3--2 and $^{13}$CO J=3--2. Since our $^{12}$CO and $^{13}$CO observations did not show any signature of a large-scale outflow or a massive envelope, the compact dust emission is likely to come from a disk around the star. The observed SED of V1094 Sco shows no distinct turnover from near infrared to millimeter wavelengths, which can be well described by a flattened disk for the dust component, and no clear dip feature around 10 \micron suggestive of absence of an inner hole in the disk. We fit a simple power-law disk model to the observed SED. The estimated disk mass ranges from 0.03 to $\gtrsim$0.12 M_\sun, which is one or two orders of magnitude larger than the median disk mass of T Tauri stars in Taurus.Comment: 18 pages, 4 figures, accepted for publication in Ap

TeachOpenCADD 2022: open source and FAIR Python pipelines to assist in structural bioinformatics and cheminformatics research

Computational pipelines have become a crucial part of modern drug discovery campaigns. Setting up and maintaining such pipelines, however, can be challenging and time-consuming-especially for novice scientists in this domain. TeachOpenCADD is a platform that aims to teach domain-specific skills and to provide pipeline templates as starting points for research projects. We offer Python-based solutions for common tasks in cheminformatics and structural bioinformatics in the form of Jupyter notebooks, based on open source resources only. Including the 12 newly released additions, TeachOpenCADD now contains 22 notebooks that cover both theoretical background as well as hands-on programming. To promote reproducible and reusable research, we apply software best practices to our notebooks such as testing with automated continuous integration and adhering to the idiomatic Python style. The new TeachOpenCADD website is available at https://projects.volkamerlab.org/teachopencadd and all code is deposited on GitHub

Photometric variability of the T Tauri star TW Hya on time scales of hours to years

MOST (Microvariability & Oscillations of STars) and ASAS (All Sky Automated Survey) observations have been used to characterize photometric variability of TW Hya on time scales from a fraction of a day to 7.5 weeks and from a few days to 8 years, respectively. The two data sets have very different uncertainties and temporal coverage properties and cannot be directly combined, nevertheless, they suggests a global variability spectrum with "flicker noise" properties, i.e. with amplitudes a ~ 1/sqrt(f), over >4 decades in frequency, in the range f = 0.0003 to 10 cycles per day (c/d). A 3.7 d period is clearly present in the continuous 11 day, 0.07 d time resolution, observations by MOST in 2007. Brightness extrema coincide with zero-velocity crossings in periodic (3.56 d) radial velocity variability detected in contemporaneous spectroscopic observations of Setiawan et al. (2008) and interpreted as caused by a planet. The 3.56/3.7 d periodicity was entirely absent in the second, four times longer MOST run in 2008, casting doubt on the planetary explanation. Instead, a spectrum of unstable single periods within the range of 2 - 9 days was observed; the tendency of the periods to progressively shorten was well traced using the wavelet analysis. The evolving periodicities and the overall flicker-noise characteristics of the TW Hya variability suggest a combination of several mechanisms, with the dominant ones probably related to the accretion processes from the disk around the star.Comment: MNRAS submitte

Cognitive loading affects motor awareness and movement kinematics but not locomotor trajectories during goal-directed walking in a virtual reality environment.

The primary purpose of this study was to investigate the effects of cognitive loading on movement kinematics and trajectory formation during goal-directed walking in a virtual reality (VR) environment. The secondary objective was to measure how participants corrected their trajectories for perturbed feedback and how participants' awareness of such perturbations changed under cognitive loading. We asked 14 healthy young adults to walk towards four different target locations in a VR environment while their movements were tracked and played back in real-time on a large projection screen. In 75% of all trials we introduced angular deviations of ±5° to ±30° between the veridical walking trajectory and the visual feedback. Participants performed a second experimental block under cognitive load (serial-7 subtraction, counter-balanced across participants). We measured walking kinematics (joint-angles, velocity profiles) and motor performance (end-point-compensation, trajectory-deviations). Motor awareness was determined by asking participants to rate the veracity of the feedback after every trial. In-line with previous findings in natural settings, participants displayed stereotypical walking trajectories in a VR environment. Our results extend these findings as they demonstrate that taxing cognitive resources did not affect trajectory formation and deviations although it interfered with the participants' movement kinematics, in particular walking velocity. Additionally, we report that motor awareness was selectively impaired by the secondary task in trials with high perceptual uncertainty. Compared with data on eye and arm movements our findings lend support to the hypothesis that the central nervous system (CNS) uses common mechanisms to govern goal-directed movements, including locomotion. We discuss our results with respect to the use of VR methods in gait control and rehabilitation